The specific objective of the research is to clone variable region gene segments V(H) from a series of rearranged mouse immunoglobulin heavy chain genes. The genetic material for these studies will come from a library of highly characterized hybridomas making monoclonal antibodies against the hemaglutinin A (HA) protein of the Influenza A virus, which has been prepared by Dr. W. Gerhard at the Wistar Institute. The clones we have chosen to study have the same or overlapping specificities against the same antigenic determinant on the (HA) protein as determined by their reactivity patterns with a panel of serum selected viral variants. The nucleotide sequences of the isolated rearranged V(H) genes will be determined and compared with each other as well as with the nucleotide sequences of the germline V(H) genes from which they are derived. This sequence data will be integrated with existing data by providing sequences for new V(H) gene families and allow us to evaluate the relative contributions of recombinational shuffling of germ line gene segments and "somatic" diversificational processes in the establishment of the immune repertoire. The studies blend the efforts of Dr. Gerhard and his group, who are using these antibodies to study antigenic variations in the HA protein, with out efforts to classify the responses of the immune system to this variation. More generally, additional information is to how the immune system works will help our understanding of any number of health related problems, e.g., auto-immune diseases, immune deficiency conditions and human myelomas.